The discovery of estrogen-dependent plasticity in the peripheral auditory system of teleost fish provides an ideal model for establishing the cellular, molecular, and neurophysiological mechanisms leading to steroid modulation of audition. Female midshipman fish use the multi-harmonic vocalizations ("hums") of males for mate localization and exhibit dramatic reproductive state-dependent shifts in the encoding of the male's hum by 8th nerve afferents that innervate the saccule, the main peripheral auditory organ in teleosts. Thus, the primary saccular afferents of reproductive females, compared to those of nonreproductive females, show an increase in best frequency and improvement in precision of temporal encoding (via phase-locking) to the upper harmonics of the male hums. Either 17-beta-estradiol or testosterone treatment of non-reproductive females for 3-5 weeks induces the enhanced auditory phenotype of reproductive females, consistent with transcriptionally-dependent events. The observed changes are likely entirely due to estrogen that circulates at 2-fold higher levels in reproductive females. In addition, auditory ganglion cells adjacent to the saccule's hair cell layer express the enzyme aromatase that converts testosterone to estrogen, and can therefore aromatize circulating testosterone to augment the locally available source of estrogen. 2 specific aims will investigate estrogen-dependent shifts in molecular (potassium channels and estrogen receptors) and neurophysiological (hair cell and primary afferent encoding) mechanisms that can lead to improvements in temporal processing via phase-locking in the auditory system. The proposed studies will also delineate mechanisms of sensorineural plasticity that are relevant to shifts in age-related hormonal states, including changes in audition that occur during the reproductive cycle and in clinical syndromes associated with abnormal patterns of hormone secretion (e.g., Turner's Syndrome). Lastly, the proposed experiments will lead to a more fundamental understanding of how deficits in the temporal encoding of acoustic signals, dependent on phase-locking mechanisms, contribute to impairments in hearing observed among humans including those with auditory neuropathy/dys-synchrony. [unreadable] [unreadable] [unreadable]